Method of producing alpha, beta-unsaturated ketosteroids carrying a methyl group on the beta-position carbon atom



United States Patent fifice 3,073,850 Patented Jan. 15, 1963 METHOD 9FPRUDUQENG u,j8-UNATURATED KETQTERUHDS CARRYING A METHYL GROUP ON THEfi-PQEHTHBN CARBON ATQM Rudolf Wiechert, Berlin-Liehterfelde, Germany,assignor to Schering A.G., Berlin, Germany No Drawing. Fiied Aug. 22,1961, Ser. No. 133,050

laims priority, application Germany Aug. 27, 1960 16 Claims. (Cl.Mil-397.4)

The present invention relates to a method of producing a, 3-unsaturatedketosteroids having a methyl group on the fi-position carbon atom, andmore particularly to the production of such compounds from apyrazolinosteroid obtained by diazomethane addition to an a,fi-UI1saturated ketosteroid.

Methods have been described for the production of a,/3-unsaturatedketosteroids which carry a methyl group on the fi-position carbon atomfrom a pyrazolino-steroid obtained by the addition of diazomethane ontothe carbon atom double bond of an a,[3-unsaturated ketone.

Thus, for example, German Patent No. 1,023,764 describes the splittingoff of nitrogen at high temperatures (about 220250 C.) from A-pyrazolines derived from 3-keto-A -steroids, and preferably carryingout this pyrolytic splitting under high vacuum. The reaction proceeds asfollows:

The crude product obtained from this method is oily and containsaccording to ultraviolet spectroscopic analysis only about 60% of thedesired 1methyl-A -3-ketosteroid, and the yield of pure compoundobtained therefrom corresponds to only about 40% of the theoretical. Afurther disadvantage of this method is that this low amount of pureyield can only be obtained if the pyrolysis reaction is itself carriedout with very pure starting material. Still a further disadvantage isthat the thermal decomposition of these pyrazolines requires operationalcriteria, particularly when carried out under high vacuum, which is verydifiicult to accomplish technically and renders the entire methoddifficult to carry out.

Attempts have been been therefore made to replace the thermal splittingof the mentioned pyrazolines by more certain and easier controllableprocedures, and for this purpose a method has been described ofutilizing acid catalysts, such as perchloric acid, fluoroboric acid orboron trifiuoride-etherate, dissolved in an organic solvent. This methodis described in the US. patent application of Wiechert et al., SerialNo. 60,812, filed Octoher 6, 1960, for Production of 1,2-Methylene and16,17- Methylene Ketosteroids. However, it was found that by this methodthe desired nitrogen splitting off can only be carried out at roomtemperature on the corresponding A -pyrazoline, and moreover, thedesired cap-unsaturated fi-methyl ketosteroids are only obtained as sideproduct and the main product which is obtained is the saturated isomericcad-methylene steroid.

Subsequently, in US. patent application of Emanuel Kaspar et al., SerialNo. 73,495, filed December 5, 1960, for Production of cap-UnsaturatedKetosteroids Having a Methyl Group on the fl-Position Carbon Atom amethod was described for the catalytic splitting ofi of nitrogen bycarrying out the method instead of in a homogeneous solution by means ofan acid catalyst on the surface of an acid adsorption agent which issuspended in an organic solvent in which the pyrazoline is only weaklyeluated.

While this method is suitable for technical production of the desiredcompound, it, however, due to the need of large amounts of adsorptionagent which must be treated in a separate step (the ratio of pyrazolinocompound to adsorption agent is about 1:50), and because of the largeamount of solvent required for eluation after the nitrogen splitting, isnot too practical for technical operation from the point of view of timeand size of operational plans.

It is accordingly a primary object of the present invention to provide amethod of producing ind-unsaturated ketosteroids having a methyl groupon the 5-position carbon atom which avoids all of the above enumerateddilficulties of the methods previously set forth for the production ofsuch compounds.

It is another object of the present invention to provide a generalmethod of producing m d-unsaturated ketosteroids having a methyl groupon the ,8-position carbon atom from pyrazolino steroids obtained bydiazomethane addition to an o e-unsaturated ketosteroid, which methodresults in the production of relatively pureB-methyl ketosteroid inrelatively high yield, and which method can be easily carried out on acommercial scale.

Other objects and advantages of the present invention will be apparentfrom a further reading of the specification and of the appended claims.

With the above and other objects in view, the present invention mainlycomprises a method of producing 04, 3- unsaturated ketosteroids having amethyl group on the i8- position carbon atom from a pyrazolino steroidobtained by diazomethane addition to an a,[3-unsaturated ketosteroid,which comprises the heating of such pyrazolino ketosteroid at apredetermined pressure at a temperature above C. with at least oneorganic base which at the predetermined pressure boils at a temperatureabove about 140 0, this method resulting in the direct splitting of thenitrogen from the pyrazolino steroid and thereby in the direct formationof the corresponding 0:,5-1111Sfltt1- rated ketosteroid having themethyl group on the fl-position carbon atom.

The splitting off of nitrogen in accordance with the present inventionis preferably carried out with an organic base such as quinoline,isoquinoline, quinaldine, collidine, lutidine, N,N-dimethylaniline,aniline, or mixtures thereof, possibly in the presence of a dilutionagent such as tetralin, at a reaction temperature of above 140 C. Inaddition to organic bases of the above type which have a boiling pointabove 140 C., it is possible to carry out the method of the presentinvention utilizing an organic base having a boiling point below 140 C.,for example pyridine, by carrying out the method under pressure so as tobe able to reach the necessary reaction temperature of about 140 C.

As will be pointed out in further detail below the method of the presentinvention is an extremely general method which is applicable to thesplitting of nitrogen from all pyrazolino steroids obtained by thediazomethane addition to an 0a,,B-I1I1Sflttlffl't6d ketosteroid. Themethod of the invention can be carried out using in general any organicbase which has a dissociation constant smaller than 10*. The mostpreferred organic bases for the carrying out of the method of thepresent invention or functionally changed hydroxyl groups or free orfunctionally changed keto groups or halogen atoms. The hydroxyl groupsmay, for example, be esterified with aliphatic, alicyclic,arylaliphatic, aromatic or heterocyclic carboxylic acids of 1-11 carbonatoms, such as acetic acid, chloroacetic acid, propionic acid, butyricacid, diethylacetic acid, enanthic acid, capronic acid, undecylenicacid, cyclopentylpropionic acid, succinic 'acid, phenylacetic acid,furancarboxylic acid, phenoxyacetic acid, caprinic acid, benzoic acid,and the like. Thus, the method of the present invention can be carriedout using as starting material a pyrazolino steriod of the formula:

Ar t l t wherein R is selected from the group consisting of H, OH andOacyl wherein acyl is derived from a lower aliphatic carboxylic acid,wherein G/ L is selected from the group consisting of a. t... A a. C CHzCH: \CH Cfi Cfi and /(JH2 Ofi CH2 and wherein Y is selected from thegroup consisting of -CHOH, CO and CHOacyl wherein acyl is derived froman organic carboxylic acid of 1-11 carbon atoms. The1,2-diazomethylene-3-ketosteroids of the present invention may bedesignated as such or as HA -pyramlino)-4',3:1,2]-3-ketosteroids.Compounds of this type, as well as 16, 17-diazomethylene-20-ketosteroidswhich may be designated as such or as [(A '-pyrazolino)-4,5':16,17ot]-20-ketosteroids may be used as starting compounds for thepresent invention. Among the suitable starting compounds may bementioned the following:

(A -pyrazo1ino)4',5:16,170; (A pregnene 3,8 ol- ZO-one-acetate) (A-pyrazolino) -4,3: 1,2aandrostane-17,8-01-3-one; (A'-pyrazolino)-4',3':I,2ut-androstane-17;9 o1 3 one- 17-acetate;

(A -pyrazolino)-4,3':1,2a-androstane-17fi ol 3 one- 17-propionate;

(A '-pyrazolino)-4,3':1,2ot-androstane-17fi-ol-3-one 17- capronate;

(A -pyrazolino)-4,3:1,2a-androstane-17p ol 3 one-17fi-cyclopentylpropionate;

(A -pyrazolino)-4,3':1,2ot-androstane-l7tt ol 3 one- 17-enanthate;

(A '-pyrazolino)-4,3:1,2u-androstane 17,3 ol 3 onel7-caprylate.

The diazomethylene starting compounds of the present invention may beproduced by the addition of diazomethylene to the correspondingketosteroid, as described in German Patent 1,023,764 and in the paper ofA. Wettstein, Helv. Chim. Acta, 27, page 1803 (1944). Thea,,B-unsaturated ketosteroids having a methyl group on the fl-positioncarbon atom produced in accordance with the method of the presentinvention may be used as intermediates in the production of othersteroids, for example by the saturation of double bonds, or, as anabolicagents, as described in the application of Kaspar et al. Serial No.73,495.

To carry out the spreading of nitrogen in accordance with the presentinvention the pyrazoline in finely divided condition is introduced intothe freshly distilled organic base, the oxygen of the air beingpreferably replaced by an inert gas, preferably nitrogen, in order toavoid the formation of undesired decomposition products, and thereaction mixture is then heated for about to 90 minutes 0 at thecorresponding reaction temperature of above 140 C., preferably at atemperature of about 170-240 C.

If a base is used for the splitting of the nitrogen which has a boilingpoint of less than 140 C., for example pyridine, the reaction is carriedout in a closed pressure vessel with small charges, for example in abomb tube, preferably at a temperature of about 200 C. after thecompletion of the reaction the reaction mixture is worked up in normalmanner. The precipitated crude product, irrespective of whether thestarting material was a melting point separated or only technically purematerial, is in the form of crystals and contains, based on ultravioletspectroscopic examination, about of the desired a,fi-unsaturatedfl-methyl-ketosteroid. After purification of the crude product in normalmanner the yield of pure compound corresponds to about 60% of thetheoretical.

The following examples are given to further illustrate the presentinvention. The scope of the invention is not, however, meant to belimited to the specific details of the examples.

Example 1 10 g. of (A '-pyrazolino)-4,3':1,2a-androstane-17fi-ol- 3-onewere added to 200 cc. of quinoline. The resulting solution is thenheated under nitrogen atmosphere to boiling for 30 minutes. Aftercooling it is diluted with ether and washed with 4 normal aqueoushydrochloric acid and then with Water until neutral. The etherealsolution is dried over sodium sulfate and after filtration from thedrying agent the other is drawn off. The thus obtained crude 1methyl-A-androstene-17B-ol-3- one (U.V.: e =10,35O) is heated on a water bathfor minutes with 30 cc. of pyridine and 18 cc. of acetanhydride. Thesolution is then stirred into ice water, the precipitate is filtered offunder suction, dried and recrystallized from isopropyl ether. There isthus obtained 1-methy1-A -androstene-17fl-o1-3-one-17-acetate having amelting point of C. The yield amounts to 60% of the theoretical.

Example 2 1 g. of (A '-pyrazolino)-4',3':1,2a-androstane-17fi-ol- 3-oneare heated in 20 cc. of quinoline for 1 hour under nitrogen atmosphereat C. and subsequently worked up as described in Example I. There isthus obtained .atmosphere in 20 cc. of aniline.

water until neutral.

l-methyl-A -androstene-175-01-3-one17-acetate melting at 140 C.

Example 3 1 g. of (A -pyrazolino)-4,3':1,2a-androstane-17fi-ol- 3-oneare heated to boiling for 1 hour under nitrogen It is then furtherworked up as described in Example 1 resulting in 1-methyl-Aandrostene-17fl-ol-3-one-17-acetate melting at 140 C.

Example 4 1 g. of (A 'pyrazolino)-4',3':1,2a-androstane-17fl-ol- 3-oneare heated for 1 hour to boiling under nitrogen atmosphere in 20 cc. ofcollidine. It is then further worked up as described in Example 1,resulting in 1- methyl-o -androstene-17B-ol-3-one-17-acetate melting at140 C.

Example 5 1 g. of (A -pyrazolino)-4,3:1,2a-cholestane-3-one in 20 cc. ofquinoline are heated under nitrogen for 30 minutes at 220230 C.Aftercooling the reaction mixture is diluted with hexane, this solutionis washed with 4 normal aqueous hydrochloric acid and then with wateruntil neutral. The hexane solution is dried over sodium sulfate andafter filtration of the drying agent the solvent is drawn off. Theresidue is recrystallized from methanol and there is obtained a1-methyl-A cholestene-3-one having a melting point of 77-78 C.

Example 6 1 g. of (A -pyrazolino)-4,3':1,2a-cholestane-3-one in 20 cc.of lutidine are heated to boiling for 1 hour under nitrogen atmosphereand subsequently further worked up as described in Example 5. Themelting point of the thus obtained 1-methy1-A -cholestene-3-one is 77-78C.

Example 7 200 mg. of (A pyrazolino) 4',3':l,2oz androstane- 178-o1-3-one and 4 cc. of pyridine are heated in a bomb tube for 1 hour at200 C. The cooled reaction mixture is subsequently taken up in ether,washed three times, each time with two normal hydrochloric acid and thenwashed with water until neutral. 'Ihe ethereal solution is dried oversodium sulfate and subsequently, after filtration of the drying agent,the solvent is evaporated under vacuum to dryness. There is thusobtained 114 mg. of a mixture of l-methyl-n -androsten'e-175-01-3-onewith a small amount of the lie-methylene compound, whichexhibits anultraviolet extinction of 6242 8530.

The purification of the crude product proceeds as describedin Example 1.

Example 8 are heated for 1 hour under nitrogen to boiling. The

solution is diluted with ether after cooling and then washed with 2normal hydrochloric acid and then With The ethereal solution is driedover sodium sulfate and after filtration of the drying agent the solventis evaporated under vacuum until dryness. The thus obtained crudeproduct is acetylated as de scribed in Example 1. There is thus obtainedl-methyl- A -androstene-17fl-ol-3-one-17-acetate having a melting pointof 140 C.

Example 9 3 g. of (A -pyrazolino)-4',5-16,17a-A-pregnene6flol-ZO-one-S-acetate in 60 cc. of quinoline are heated for 30minutes to 160l70 C. The solution is, after cooling, diluted with ether,washed with 4 normal aqueous hydrochloric acid and then with water untilneutral. The ethereal solution is dried over sodium sulfate and afterfiltration of the drying agent the solvent is evaporated in vacuum untildryness. The residue is recrystallized from ethyl acetate. There, isthus obtained 1.9 g.

having a melting point of 171 C., and exhibiting an ultravioletextinction of e =8750.

Without further analysis, the foregoing will so fully reveal the gist ofthe present invention that others can by applying current knowledgereadily adapt it for various applications without omitting featuresthat, from the standpoint of prior art, fairly constitute essentialcharacteristics of the generic or specific aspects of this inventionand, therefore such adaptations should and are intended to becomprehended within the meaning and range of equivalence of thefollowing claims.

What is claimed as new and desired to be secured by Letters Patent is:

1. Method of producing il-unsaturated ketosteroids having a methyl groupon the ii-position carbon atom from a pyrazolino-steroid obtained bydiazo-methane addition to an t -unsaturated ketosteroid, which comprisesheating said pyrazolino-steroid at a predetermined pressure at atemperature above about C. with at least one organic base which at saidpredetermined pressure boils at a temperature above about 140 C. so asto split the nitrogen from said pyraZolino-steroid and thereby form thecorresponding n e-unsaturated ketosteroid having a methyl group on the(i-position carbon atom.

2. Method of producing a,fi-unsaturated ketosteroids having a methylgroup on the B-position carbon atom from a pyrazolino-steroid obtainedby diazomethane ad dition to an nap-unsaturated ketosteroid, whichcomprises heating said pyrazolino-steroid at atmospheric pressure at atemperature above about 140 C. with at least one organic base which atsaid atmospheric pressure boils at a temperature above about 140 C. soas to split the nitrogen from said pyrazolino-steroid and thereby formthe corresponding ego-unsaturated ketosteroid having a methyl group onthe B-position carbon atom.

3. Method of producing m d-unsaturated ketosteroids having a methylgroupon the fi-position carbon atom from a pyrazolino-steroid obtainedby diazomethane addition to an a,,8-unsaturated ketosteroid, whichcomprises heating said pyrazolino-steroid at a predetermined pressure ata temperature of about -240 C. with at least one organic base which atsaid predetermined pressure boils at a temperature above about 170 C. soas to split the nitrogen from said pyrazolino-steroid and thereby formthe corresponding 0a,]3-UI1Sfl-tll121t6d ketosteroid having a methylgroup on the ,B-position carbon atom.

4. Method of producing anti-unsaturated ketosteroids having a methylgroup on the l3-posi-tion carbon atom from a pyrazolino-steroid obtainedby diazomethane addition to an cap-unsaturated ketosteroid, whichcomprises heating said pyrazolino-steroid at a predetermined pressure ata temperature above about 140 C. with at least one organic base which atsaid predetermined pressure boils at a temperature above about 140 C. inan atmos phere of a gas inert to the reactants so as to split thenitrogen from said pyrazolino-steroid and thereby form the correspondingaft-unsaturated ketosteroid having a methyl group on the fi-positioncarbon atom.

5. Method of. producing a,/8-unsaturated ketosteroids having a methylgroup on the B-position carbon atom from a pyrazolino-steroid obtainedby diazomethane addition to an m tt-unsaturated ketosteroid, whichcomprises heating said pyrazolino-steroid at a predetermined pressure ata temperature above about 140 C. with at least one organic base which atsaid predetermined pressure boils at a temperature above about 140 C.and having a dissociation constant of less than 10- so as to split thenitrogen from said pyrazolino-steroid and thereby form the correspondingcad-unsaturated ketosteroid having a methyl group on the [3-positioncarbon atom.

6. Method of producing a,,8-unsaturated ketosteroids having a methylgroup on the ,B-position carbon atom from a pyrazolino-steroid obtainedby diazomethane addition to an oafi unsaturated ketosteroid, whichcomprises heating said pyrazolino-steroid at atmospheric pressure at atemperature above about 140 C. with at least one organic base which atsaid atmospheric pressure boils at a temperature above about 140 C. andhaving a dissociation constant of less than 10'- so as to split thenitrogen from said pyrazolino-steroid and thereby form the correspondingvi e-unsaturated ketosteroid having a methyl group on the fi-positioncarbon atom.

7. Method of producing a,fl-unsaturated ketosteroids having a methylgroup on the B-position carbon atom from a pyrazolino-steroid obtainedby diazomethane addition to an a,fi-unsaturated ketosteroid, whichcomprises heating said pyrazolino-steroid at a predetermined pressure ata temperature above about 140 C. with at least one organic base which atsaid predetermined pressure boils at a temperature above about 140 C.and being selected from the group consisting of quinoline, isoquinoline,quinaldine, collidine, lutidine, N,N-dimethylaniline, aniline andpyridine so as to split the nitrogen from said pyrazolinosteroid andthereby form the corresponding n p-unsaturated ketosteroid having amethyl group on the fi-position carbon atom.

8. Method of producing c p-unsaturated ketosteroids having a methylgroup on the fi-position carbon atom from a pyrazolino-steroid obtainedby diazomethane addition to an 2,5-UI1S8tUlflt6d ketosteroid, whichcomprises heating said pyrazolino-steroid at atmospheric pressure at atemperature above about 140 C. with quinoline so as to split thenitrogen from said pyrazolino-steroid and thereby form the correspondingc p-unsaturated ketosteroid having a methyl group on the .8-positioncarbon atom.

9. Method of producing ix-unsaturated ketosteroids having a methyl groupon the fi-position carbon atom form a pyrazolino-steroid obtained bydiazomethane addiiton to an n g-unsaturated ketosteroid, which comprisesheating said pyrazolino-steroid at atmospheric pressure at a temperatureabove about 140 C. with aniline so as to split the nitrogen from saidpyrazolino-steroid and thereby form the corresponding e g-unsaturatedketosteroid having a methyl group on the ,B-position carbon atom.

10. Method of producing e g-unsaturated ketosteroids having a methylgroup on the St-position carbon atom from a pyrazolino-steroid obtainedby diazomethane addition to an a,;8-unsaturated ketosteroid, whichcomprises heating said pyrazolinosteroid at superatmospheric pressure ata temperature above about 140 C. with pyridine so as to split thenitrogen from said pyrazolino-steroid and thereby form the correspondinga,l3-1111S21U.1I&t6d ketosteroid having a methyl group on thefi-position carbon atom.

11. Method of producing v n-unsaturated ketosteroids having a methylgroup on the fi-position carbon atom from a pyrazolino-steroid obtainedby diazomethane addition to an a,;-unsaturated ketosteroid, whichcomprises heating a pyrazolino-steroid of the formula:

wherein X is selected from the group consisting of alkyl,

(OH (Oacyl and \/OH H H *alkyl wherein acyl is derived from an organiccarboxylic acid of 1-11 carbon atoms at a predetermined pressure at atemperature above about 140 C. with at least one organic base which atsaid predetermined pressure boils at a temperature above about 140 C. soas to split the nitrogen from said pyrazolinosteroid and thereby formthe corresponding a s-unsaturated ketosteroid having a methyl group onthe fi-position carbon atom.

12. Method of producing 0a,;3-l11'18311lf3tfid ketosteroids having amethyl group on the ,B-position carbon atom from a pyrazolino-steroidobtained by diazomethane addition to an c p-unsaturated ketosteroid,which comprises heating a pyrazolino-steroid of the formula:

wherein X is selected from the group consisting of alkyl,

(OH (OacyI and (0H wherein acyl is derived from an organic carboxylicacid of 1-11 carbon atoms at a predetermined pressure at a temperatureabove about C. with at least one organic base which at saidpredetermined pressure boils at a temperature above about 140 C. andhaving a dissociation constant of less than 10- so as to split thenitrogen from said pyrazolino-steroid and thereby form the correspondingogfi-UIlSfliUffllfiid ketosteroid having a methyl group on thefl-position carbon atom.

13. Method of producing t g-unsaturated ketosteroids having a methylgroup on the fl-position carbon atom from a pyrazolino-steroid obtainedby diazomethane addition to an e g-unsaturated ketosteroid, whichcomprises heating a pyrazolino-steroid of the formula:

wherein X is selected from the group consisting of alkyl, (0H (oacyl and(011 H -alkyl wherein acyl is derived from an organic carboxylic acid of1-11 carbon atoms at a predetermined pressure at a temperature aboveabout 140 C. with at least one organic base which at said predeterminedpressure boils at a temperature above about 140 C. and being selectedfrom the group consisting of quinoline, isoquinoline, quinaldine,collidine, lutidine, N,N-dimethylaniline, aniline and pyridine so as tosplit the nitrogen from said pyrazolinosteroid and thereby form thecorresponding c p-unsaturated ketosteroid having a methyl group on thefi-position carbon atom.

14. Method of producing a,fl-unsaturated ketosteroids having a methylgroup on the fi-position carbon atom from a pyrazolino-steroid obtainedby diazomethane addition to an cap-unsaturated ketosteroid, whichcomprises heating a pyrazolino-steroid of the formula:

phatic carboxylic acid, wherein wherein R is selected from the groupconsisting of H, OH and Oacyl wherein acyl is derived from a loweraliphatic carboxylic acid, wherein is selected from the group consistingof (BH'CHQ en and wherein Y is selected from the group consisting ofCHOH CO and -CHOacyl wherein acyl is derived from an organic carboxylicacid of 1-11 carbon atoms at a predetermined pressure at a temperatureabove about 140 C. with at least one organic base which at saidpredetermined pressure boils at a temperature above about 140 C. so asto split the nitrogen from said pyrazolinosteroid and thereby form thecorresponding a,;8-unsaturated ketosteroid having a methyl group on thefl-p'osition carbon atom.

15. Method of producing cap-unsaturated ketosteroids having a methylgroup on the 5-position carbon atom from a pyrazolino-steroid obtainedby 'diazomethane addition to an a,/8-unsaturated ketosteroid, whichcomprises heat- &

and

ing a pyrazolino-steroid of the formula:

G L p I p i V wherein R isselegted from, the group consisting of H, OHand Oacyl wherein acyl is derived from a lower aliis selected from thegroup consisting of (EH/ta (E1: 5

I on

and wherein Y is selected from the .group consisting of CHOH, CO andCHOacy1 wherein acyl is derived from an organic carboxylic acid of 1-11carbon atoms at a predetermined pressure at a temperature above about C.with at least one organic base which at'said predetermined pressureboils at a temperature above about 140 C. and having a dissociationconstant of less than 10- so as to split the nitrogen from saidpyrazolinosteroid and thereby form the corresponding a,fi-unsaturatedketosteroid having a methyl group on the fl-position carbon atoms.

16. Method of producing tsp-unsaturated ketosteroids having a methylgroup on the ,B-position carbon atom from a pyrazolino-steroid obtainedby diazomethane addition to an a e-unsaturated ketosteroid, whichcomprises heating a pyrazolino-steroid of the formula:

wherein R is selected from the group consisting of H,

cm on o o and and wherein Y selected from the group consisting of I CHOH-CO and CHOacyl-wherein acyl is derived from an organic carboxylic acidof '1-11 carbon atoms at a predetermined pressure at a temperature aboveabout 140 C. withfat leastrone organic base which-at s'aid'predeterrnined pressure boils ata temperature above about I 140 C. andbeing selected'from the group consisting of quinoline, isoquinoline,quinaldine, I collidine, flutidine,

N,N-dimethylaniline, aniline and pyridineso as to split I .the' nitrogen.from saidpyrazolinosteroid and thereby f form the correspondingaim-unsaturated ketosteroid having .a'methyl group on the B-positioncarbon atom; i

' No references cited.

1. METHOD OF PRODUCING A,B-UNSATURATED KETOSTEROIDS HAVING A METHYLGROUP ON THE B-POSITION CARBON ATOM FROM A PYRAZOLINO-STEROID OBTAINEDBY DIAZOMETHANE ADDITION TO AN A,B-UNSATURATED KETOSTEROID, WHICHCOMPRISES HEATING SAID PYRAZOLINO-STEROID AT A PREDETERMINED PRESSURE ATA TEMPERATURE ABOVE ABOUT 140* C. WITH AT LEAST ONE ORGANIC BASE WHICHAT SAID PREDETERMINED PRESSURE BOILS AT A TEMPERATURE ABOVE ABOUT 140 C.SO AS TO SPLIT THE NITROGEN FROM SAID PYRAZONLINO-STEROID AND THEREBYFORM THE CORRESPONDING A,B-UNSATURATED KETOSTERIOD HAVING A METHYL GROUPON THE B-POSITION CARBON ATOM.